Notch and BCR signaling synergistically promote the proliferation of Raji B-lymphoma cells.
The evolutionarily conserved Notch signaling pathway plays a pivotal role in cell proliferation, apoptosis, and cell fate decision from invertebrates to vertebrates, and is oncogenic in some human hematopoietic malignancies. To study the role of Notch signaling in B-lymphoma, we expressed a soluble fragment of human Delta-like1 (hDll1) in E. coli, which was shown to activate the Notch signaling. Incubation of Burkitt's lymphoma Raji cells with the soluble hDll1 led to gamma-secretase-dependent up-regulation of a Notch downstream gene, Hes1. This treatment synergized with B-cell receptor (BCR)-mediated signaling to promote proliferation of Raji cells in vitro, which was cancelled by GSI. We further showed that Notch signaling significantly repressed, while gamma-secretase inhibitor (GSI) enhanced, "natural" apoptosis of Raji cells. Because c-myc is a downstream gene of both Notch signaling and BCR signaling, and GSI blocked c-myc expression in the presence of hDll1 and anti-IgM, Notch signaling might interact with BCR signaling at the level of c-myc expression to regulate proliferation and apoptosis of B-lymphoma cells.
He
Fei
F
Department of Medical Genetics and Developmental Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xian, China.
Wang
Li
L
Hu
Xing-Bin
XB
Yin
Dan-Dan
DD
Zhang
Ping
P
Li
Guo-Hui
GH
Wang
Yao-Chun
YC
Huang
Si-Yong
SY
Liang
Ying-Min
YM
Han
Hua
H
D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology*; D051562:Proto-Oncogene Proteins c-bcr / Q000378:metabolism / Q000502:physiology*; D051880:Receptors, Notch / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D017931:DNA Primers; D051880:Receptors, Notch; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr